tbuckley/cabot-search huggingface dataset:
AB1471 EVALUATION OF CXCL13 SERUM LEVELS IN A COHORT OF PATIENTS WITH PERIPHERAL PSORIATIC ARTHRITIS IN COMPARISON WITH RHEUMATOID ARTHRITIS.
Authors: S. Piantoni, F. Angeli, F. Regola, L. Valtellini, F. Franceschini, P. Airò
Journal: Annals of the Rheumatic Diseases (2022)

Background The research of circulating biomarkers in the field of chronic arthritis is still an unmet need, especially for the subgroup of seronegative arthritis [e.g., negative for anti-citrullinated peptides autoantibodies (ACPA) and/or rheumatoid factors (RF)]. In fact, in this clinical subset, there is a lack of soluble molecules which could help for a diagnostic or prognostic purpose, and the differential diagnosis between psoriatic arthritis (PsA) and seronegative rheumatoid arthritis (RA) is still a challenge. C-X-C motif chemokine 13 (CXCL13) is one of the most promising biomarkers recently identified, because of its association with active synovitis (1) and with a poor prognosis in RA (2), although there are still inadequate results to justify its routine use. No data are available of the determination of CXCL13 serum levels in PsA. Objectives To analyze CXCL13 serum levels in a cohort of PsA patients with a history of peripheral involvement in comparison with RA. Methods Cross sectional analysis of consecutive patients with peripheral PsA [n:81; male/female=44/37; median age (25°-75° percentile)=54 (46-62) years; 28-joint Disease Activity Score-C Reactive Protein (CRP-DAS28)=1.9 (1.6-2.5); active psoriasis=43%; DAPSA (Disease Activity in PSoriatic Arthritis) score=8 (3-14)] and RA [n:143; male/female=30/113; age =62 (50-70) years; seropositive=67%; CRP-DAS28=2.1 (1.5-2.8)] was performed. 100 sex and age-matched healthy controls (HC) were enrolled. CXCL13 serum levels were assessed through commercial ELISA test (R&amp;D). Results CXCL13 serum levels were higher in all the subgroups of patients [PsA: 50.9 (34.5-80.2) pg/mL, p&lt;0.01; RA: 77.2 (52.9-107.7) pg/mL, p&lt;0.01; RA ACPA+: 77.7 (55.9-110.7) pg/mL, p&lt;0.01; RA ACPA-: 69.5 (49.3-104) pg/mL, p&lt;0.01] than in HC (22.3 (17.7-33.8) pg/mL). No significant differences were found among RA patients according with their seropositivity (p=0.378). CXCL13 serum levels were lower in PsA patients than in RA patients, independently from their seropositivity [vs RA ACPA+, p&lt;0.01; vs RA ACPA-, p=0.012]. CXCL13 serum levels were positively correlated with CRP in PsA patients (r=0.30; p=0.008), but not with DAPSA score. Conclusion These results confirm the value of CXCL13 as a biomarker in the field of chronic arthritis. Its higher levels in seronegative RA than in PsA suggests its possible value in the differential diagnosis of these two subsets of arthritis. References [1]Bechman et al. BMC Rheumatology 2020; [2]Bugatti et al. Rheumatology 2014. Disclosure of Interests None declared
AB0274 PRESCRIPTION, SWITCH RATE AND THERAPEUTIC RESPONSE DURING BIOLOGIC THERAPY IN INFLAMMATORY RHEUMATIC DISEASES: AN OBSERVATIONAL STUDY IN SOUTHERN MOROCCO
Authors: H. Tebaa, F. Idrissi Zaki, H. Arabi, A. Mougui, I. El Bouchti
Journal: Annals of the Rheumatic Diseases (2022)

Background The use of biological treatment has improved the prognosis of patients with rheumatic diseases. It is important to know the different effects leading to switch in order to adapt the prescription to the patients’ profile. Objectives To study the prescription profile of biological agents (bDMARD) during chronic inflammatory rheumatic diseases, their impact on disease activity, frequency and causes of switch. Methods This is a retrospective study including 106 patients followed for chronic inflammatory rheumatism treated by biological agents. Results We included 106 patients, sex ratio (0.44), mean age was 41.5 (±12 .97). 64.4% were followed for spondyloarthritis (41 cases of ankylosing spondylitis, 10 cases of psoriatic arthritis, 11 cases of spondyloarthritis and chronic inflammatory bowel disease). 35.6% of the cases had rheumatoid arthritis, Seropositive in 32%, associated with (Sjorgen’s syndrome in 7.5% of cases, lupus in 1.9% of cases, vasculitis in 2% of cases). The mean time between diagnosis and initiation of biotherapy was 54 months (±57.34). The first biologic prescribed for rheumatoid arthritis was Rituximab (94%), Infliximab was the first choice for spondyloarthritis (71%). Conventional treatment was combined with biotherapy in 79% versus 21% just treated by a biological treatment, the switch rate was high in the in the group receiving monotherapy with a significant difference (P=0.024). The initial mean DAS-28 and BASDAI were 4.01 (±2.12) and 4.76 (±2.2) respectively, versus 2.45 (±1.98) and 3.78 (±2.01) after initiation of biologic therapy (P=0.0082). The first cause of switch was therapeutic escape in (82.36%), followed by ineffectiveness in (11.76%) and a paradoxical reaction such as skin psoriasis in (5.85%). Switching was made to an Anti TNF alpha in 14 patients and to another therapeutic class in 3 patients. Conclusion Regular monitoring of the efficacy and tolerance of biological treatment is an integral part of the management of chronic inflammatory rheumatism. References [1] Gottenberg J, Morel JJ, Perodeau E, Bardin T, Combe B, Dougados M, et al. Comparative effectiveness of rituximab, abatacept, and tocilizumab in adults with rheumatoid arthritis and inadequate response to TNF inhibitors: prospective cohort study. BMJ. 2019 Jan 24 [2] Brkic A, Diamantopoulos AP, Haavardsholm EA, Fevang BTS, Brekke LK, Loli L, et al. Exploring drug cost and disease outcome in rheumatoid arthritis patients treated with biologic and targeted synthetic DMARDs in Norway in 2010–2019 – a country with a national tender system for prescription of costly drugs. BMC Health Serv Res. 2022 Dec;22(1) [3] Wang Z, Huang M, Yu B, Huang Y, Zheng S, Yang X, et al. Comparison of the efficacy and safety indicators of DMARDs for rheumatoid arthritis. Medicine. 2021 Jul 23;100(29):e26524. Disclosure of Interests None declared
AB0070 INHIBITION OF STAT3 IN PBMCs FROM RHEUMATOID ARTHRITIS PATIENTS: CLUES TO UNDERSTAND SELECTIVITY OF JANUS KINASE INHIBITORS
Authors: F. Cacciapaglia, V. Venerito, S. del Vescovo, S. Stano, R. Bizzoca, D. Natuzzi, N. Lacarpia, M. Fornaro, F. Iannone
Journal: Annals of the Rheumatic Diseases (2022)

Background The Janus kinase (Jak) - signal transducer and activator of transcription (STAT) pathway has 4 Jak proteins and 7 STAT factors that mediate intracellular downstream of cytokine receptors. Targeted small-molecule therapies with different bond affinity to Jak proteins have been demonstrated effective in rheumatoid arthritis (RA) treatment, but the clinical significance of selective inhibition remains unclear. Objectives To explore the effect of selective inhibition of Jak-STAT pathway in peripheral blood mononuclear cells (PBMC) from RA patients compared to healthy donors (HD). Methods In vitro Jak inhibition of the subunit 3 of phosphorylated (p) than activated STAT was measured by flow cytometry in peripheral blood mononuclear cells (PBMC) from RA patients with active disease (DAS28&gt;5.1) naïve to any DMARDs (n.5) and HD (n.5), following recombinant human 0.1 ng/ml IL-6 (Peprotech – NJ, USA) stimulation. After blood separation, PBMC were overnight incubated with IC50 concentrations of selective Jak1-, Jak2-, Jak3- and Tyk2-inhibitors (Biovision Inc. – CA, USA) with or without IL-6 stimulation. Mean fold-increase of pSTAT3 was then compared in presence of different compounds stimulation. Results Mean pSTAT3 activity after overnight incubation was significantly higher in RA patients compared to HD (37%; 95CI 8.2-56.7 vs 17.9%; 95CI 4.6-21 – p=0.01). After IL-6 stimulation, a 2-fold and a 1.4-fold increase in pSTAT3 levels was observed in PBMC from RA patients and HD, respectively. In unstimulated PBMC from HD Jak-inhibitors didn’t significantly reduced pSTAT3 activity. In CD14+ cells from RA patients, pSTAT3 activity was reduced with no differences between all four selective Jak-inhibitors, while in CD4+ cells only Jak1-inhibition was able to reduce by 40% pSTAT3 activity. After IL-6 stimulation, the co-culture with Jak1- or JaK3- selective inhibitors was able to significantly reduce pSTAT3 levels in CD4+ lymphocytes, by an average of 20%. While in CD14+ monocytes Jak1-, Jak2- and Jak3- selective inhibitors were able to reduce pSTAT3 activity by a mean of 30%. Tyk-2 selective inhibitor did not interfere with STAT3 activation by IL-6 stimulation of PBMC from RA patients and HD. Conclusion Jak/STAT3 activity of PBMC from RA patients with active disease may be differently modulated by specific inhibitors. Selectivity of Jak-inhibitors seems more relevant in lymphocytes after IL-6 stimulation. These preliminary findings may explain discrepancies in effectiveness of selective Jak-inhibitors and pave the way for different choices in clinical practice. References [1]Tanaka Y, et al. Nat Rev Rheumatol. 2022 Jan 5:1–13. [2]Traves PG, et al. Ann Rheum Dis. 2021 Jul;80(7):865-875. [3]Choy EH. Rheumatology (Oxford). 2019 Jun 1;58(6):953-962. Disclosure of Interests None declared
AB0677 Frequency and risk factors of osteoporosis in fertile women with systemic scleroderma
Authors: A. Sorokina, O. Dobrovolskaya, O. Nikitinskaya, N. Demin, N. Toroptsova
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To determine the frequency and risk factors of osteoporosis (OP) in fertile women with systemic scleroderma (SSс) Methods 64 women (36,0 [31,5; 43,5] years old) with SSс were enrolled in the study: 35 (54,7%) with limited and 29 (45,3%) with diffuse cutaneous subtype without overlap rheumatic syndromes. The median disease duration was 5,0 [2,0; 9,0] years. Glucocorticoids (GC) were taken by 49 (76,6%) patients with the median duration of treatment 5,0 [2,0; 10,0] years. Dual energy X–ray absorptiometry (DXA) of the lumbar spine, the femoral neck and the total hip was performed. To estimate the value of the BMD the Z-score was used. Low BMD was considered at a Z-score &lt; -2.0 SD. A univariate logistic regression analysis was performed to analyze the factors associated with OP. Results Low BMD was detected in 8 (12.5%) patients. 5 (7,8%) women had a history of low-trauma fracture, among them only 1 (1,6%) patient had low BMD and 4 (6,2%) persons - normal BMD. A univariate logistic regression was performed to identify OP risk factors. Among traditional risk factors, low body mass index (BMI) associated with OP (OR 1,39 [1.04; 1.88], p=0,03) and falls during the past year (OR 5,25 [1.04; 26.36], p=0,04). Among specific ones – duration of SSc (OR 1,19 [1.02; 1.39], p=0,02), duration of GC using (OR 1,11 [1.00; 1.23], p=0,04), hand joint contractures (OR 8,54 [1.41; 51.63], p=0,02). There was no effect of smoking, treatment with proton pump inhibitors, family history of osteoporosis, age, subtype SSc, modified Rodnan score, digital ulcer, cutaneous calcification, esophageal hypotension, interstitial lung disease, diffusing capacity of the lung for carbon monoxide, force vital capacity, CRP, erythrocyte sedimentation rate, creatinine, presence of antinuclear antibody, anticentromere antibody or antitopoisomerase I antibody on the development of OP in fertile women with SSс. Conclusion Low BMD was detected in 12.5% of fertile women with SSс. Low BMI, falls during the past year, duration of SSs and GC taking, hand joint contractures associated with OP. Disclosure of Interests None declared
AB1219 ASSOCIATION OF CAROTID ATHEROSCLEROSIS WITH SARCOPENIA IN MALE PATIENTS WITH CORONARY ARTERY DISEASE
Authors: M. Letaeva, O. Malyshenko, M. Koroleva, J. Averkieva, T. Raskina
Journal: Annals of the Rheumatic Diseases (2022)

Objectives To investigate the association between sarcopenia and carotid atherosclerosis in male patients with coronary artery disease (CAD). Methods Here we enrolled 79 male patients with CAD verified by coronary angiography (median age = 63 (57; 66) years). Sarcopenia was diagnosed according to the recommendations of the European Working Group on Sarcopenia in Older People (EWGSOP, 2010) by examining muscle strength, muscle mass, and muscle function. Severity of carotid atherosclerosis was assessed by color duplex scanning by measuring intima-media thickness and percent stenosis. Patients were then divided into those without sarcopenia (n = 31), with pre-sarcopenia (n = 21), and sarcopenia (n = 27). Results Patients with sarcopenia had significantly higher intima-media thickness than those without sarcopenia (p = 0.005). Multiple carotid plaques and &gt; 50% stenosis were significantly more frequent in patients with sarcopenia compared with those with pre-sarcopenia (48.15% versus 9.50%, p = 0.015) and without sarcopenia (48.15 % versus 12.90%, p = 0.013). Severity of carotid atherosclerosis negatively correlated with musculoskeletal index (r = -0.227, p = 0.047). Conclusion Severe carotid atherosclerosis was associated with a decrease in muscle mass, suggesting a link between atherosclerosis and sarcopenia and potentially elevated risk of adverse outcomes in patients with a sarcopenia comorbidity. Disclosure of Interests None declared
International electronic health record-derived post-acute sequelae profiles of COVID-19 patients
Authors: Harrison G. Zhang, Arianna Dagliati, Zahra Shakeri Hossein Abad, Xin Xiong, Clara-Lea Bonzel, Zongqi Xia, Bryce W. Q. Tan, Paul Avillach, Gabriel A. Brat, Chuan Hong, Michele Morris, Shyam Visweswaran, Lav P. Patel, Alba Gutiérrez-Sacristán, David A. Hanauer, John H. Holmes, Malarkodi Jebathilagam Samayamuthu, Florence T. Bourgeois, Sehi L’Yi, Sarah E. Maidlow, Bertrand Moal, Shawn N. Murphy, Zachary H. Strasser, Antoine Neuraz, Kee Yuan Ngiam, Ne Hooi Will Loh, Gilbert S. Omenn, Andrea Prunotto, Lauren A. Dalvin, Jeffrey G. Klann, Petra Schubert, Fernando J. Sanz Vidorreta, Vincent Benoit, Guillaume Verdy, Ramakanth Kavuluru, Hossein Estiri, Yuan Luo, Alberto Malovini, Valentina Tibollo, Riccardo Bellazzi, Kelly Cho, Yuk-Lam Ho, Amelia L. M. Tan, Byorn W. L. Tan, Nils Gehlenborg, Sara Lozano-Zahonero, Vianney Jouhet, Luca Chiovato, Bruce J. Aronow, Emma M. S. Toh, Wei Gen Scott Wong, Sara Pizzimenti, Kavishwar B. Wagholikar, Mauro Bucalo, Tianxi Cai, Andrew M. South, Isaac S. Kohane, Griffin M. Weber
Journal: npj Digital Medicine (2022)

The risk profiles of post-acute sequelae of COVID-19 (PASC) have not been well characterized in multi-national settings with appropriate controls. We leveraged electronic health record (EHR) data from 277 international hospitals representing 414,602 patients with COVID-19, 2.3 million control patients without COVID-19 in the inpatient and outpatient settings, and over 221 million diagnosis codes to systematically identify new-onset conditions enriched among patients with COVID-19 during the post-acute period. Compared to inpatient controls, inpatient COVID-19 cases were at significant risk for angina pectoris (RR 1.30, 95% CI 1.09-1.55), heart failure (RR 1.22, 95% CI 1.10-1.35), cognitive dysfunctions (RR 1.18, 95% CI 1.07-1.31), and fatigue (RR 1.18, 95% CI 1.07-1.30). Relative to outpatient controls, outpatient COVID-19 cases were at risk for pulmonary embolism (RR 2.10, 95% CI 1.58-2.76), venous embolism (RR 1.34, 95% CI 1.17-1.54), atrial fibrillation (RR 1.30, 95% CI 1.13-1.50), type 2 diabetes (RR 1.26, 95% CI 1.16-1.36) and vitamin D deficiency (RR 1.19, 95% CI 1.09-1.30). Outpatient COVID-19 cases were also at risk for loss of smell and taste (RR 2.42, 95% CI 1.90-3.06), inflammatory neuropathy (RR 1.66, 95% CI 1.21-2.27), and cognitive dysfunction (RR 1.18, 95% CI 1.04-1.33). The incidence of post-acute cardiovascular and pulmonary conditions decreased across time among inpatient cases while the incidence of cardiovascular, digestive, and metabolic conditions increased among outpatient cases. Our study, based on a federated international network, systematically identified robust conditions associated with PASC compared to control groups, underscoring the multifaceted cardiovascular and neurological phenotype profiles of PASC.
AB1155 PAUSING METHOTREXATE IMPROVES IMMUNOGENICITY OF COVID-19 VACCINATION IN PATIENTS WITH RHEUMATIC DISEASES
Authors: A. N. Arumahandi de Silva, L. M. Frommert, F. Albach, J. Klotsche, V. Scholz, A. Ten Hagen, L. M. Jeworowski, T. Schwarz, J. Zernicke, V. M. Corman, C. Drosten, G. R. Burmester, R. Biesen
Journal: Annals of the Rheumatic Diseases (2022)

Background Several research groups have recently described a reduced vaccination response to COVID-19 vaccination under methotrexate (MTX) (1,2). The increase in humoral immune response when pausing MTX two weeks after vaccination has already been described for influenza vaccination (3). However, data regarding MTX-hold during COVID-19 vaccination are still lacking. Objectives To study the effect of MTX and its discontinuation on the humoral immune response after COVID-19 vaccination in patients with autoimmune rheumatic diseases (AIRD). Methods In this retrospective study, neutralising SARS-CoV-2 antibodies were measured after second vaccination in 64 rheumatic patients on methotrexate therapy, 31 of whom temporarily paused medication without a fixed regimen. The control group consisted of 21 AIRD patients without immunosuppressive medication. Results MTX patients showed a significantly lower mean antibody response compared to AIRD patients without immunosuppressive therapy (71.8 % vs 92.4 %, p&lt;0.001). For patients taking MTX, age correlated negatively with immune response (r=-0.49; p&lt;0.001). All nine patients with antibody levels below the cut-off were older than 60 years. Patients who held MTX during at least one vaccination showed significantly higher mean neutralising antibody levels after second vaccination, compared to patients who continued MTX therapy during both vaccinations (83.1 % vs 61.2 %, p=0.001). This effect was particularly pronounced in patients older than 60 years (80.8 % vs 51.9 %, p=0.001). The impact of the time period after vaccination was greater than of the time before vaccination with the critical cut-off being 10 days. Conclusion MTX reduces the immunogenicity of SARS-CoV-2 vaccination in an age-dependent manner. Our data further suggest that holding MTX for at least 10 days after vaccination significantly improves the antibody response in patients over 60 years of age. References [1]Haberman RH, Herati R, Simon D, et al. Methotrexate hampers immunogenicity to BNT162b2 mRNA COVID-19 vaccine in immune-mediated inflammatory disease. Annals of the Rheumatic Diseases 2021 [2]Mahil SK, Bechman K, Raharja A, et al. The effect of methotrexate and targeted immunosuppression on humoral and cellular immune responses to the COVID-19 vaccine BNT162b2: a cohort study. The Lancet Rheumatology 2021;3(9):e627-e37. [3]Park JK, Choi Y, Winthrop KL, et al. Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: post hoc analysis of a randomised clinical trial. Annals of the rheumatic diseases 2019;78(9):1283-84. Acknowledgements We would like to thank Tanja Braun and Vera Höhne-Zimmer for their support in obtaining the ethics vote and for their organisational support. Disclosure of Interests None declared
POS1371 HYPOMETHYLATION OF CIRCULATING IMMUNE CELLS IN PATIENTS WITH GRAVES’ ORBITOPATHY – A PRELIMINARY STUDY
Authors: V. Kaskova, A. Petráčková, J. Schovánek, M. Karhanova, J. Savara, E. Kriegova
Journal: Annals of the Rheumatic Diseases (2022)

Background Graves’ orbitopathy (GO) is an eye disease occurring in patients with autoimmune thyroid disorders (AITD), most commonly Graves´ disease. It is characterized by inflammation affecting soft tissues of the orbit. A recent study demonstrated an association between fibroblast hypomethylation and disease activity in GO (Virakul et al ., Front Endocrinol, 2021). Because procurement of fibroblast from GO patients require an invasive sampling, we wondered whether analysis of global DNA methylation in circulating immune cells obtained from peripheral blood could contribute to early detection of GO from patients with AITD. Objectives To compare global DNA methylation pattern in circulating immune cells obtained from AITD patients with GO and without GO history and healthy controls. Methods Global DNA methylation was quantified in circulating immune cell populations by flow cytometry using 5-methylcytosine antibody in patients with GO (n=10), AITD without GO history (n=9) and healthy controls (n=8). Immune populations (CD4 + and CD8 + T cells, B cells, monocytes and CD56 dim/bright NK cells) and their activation status were identified using CD3/4/8/14/16/19/25/45/56/69 antibodies. Results In patients with GO, global DNA methylation was reduced by ~50% in the activated (CD25 + ) CD8 + T cells and by ~35% in the whole CD8 + T cell population compared to patients with AITD (p=0.006). Moreover, percentage of CD8 + T cells, but not activated subpopulation, was higher in GO when compared to AITD (p=0.04). Hypomethylation by ~20% was detected in monocytes as well as in CD56 dim NK cells and their activated (CD69 + ) subpopulation when GO was compared with AITD (p≤0.02). Of these cell populations, percentage of monocytes was also higher in GO when compared to AITD (p=0.04). Global methylation in B cells, CD4 + T cells and CD56 bright NK cells did not differ between patients with GO and patients with AITD (p&gt;0.05). Of these populations, higher percentage of B cells was detected in GO when compared to AITD group (p=0.02). Analysis of larger patient cohorts is in progress with particular emphasis on the relationship of methylation patterns to GO disease activity. Conclusion This is the first study identifying the different global methylation profile of circulating immune cells in patients with GO characterized by DNA hypomethylation in CD8 + T cells, CD56 dim NK cells and monocytes compared to patients with AITD. Our study nominates hypomethylation as a non-invasive biomarker of GO and should be validated in a larger cohort of patients. Acknowledgements MH CZ NU21J-01-00017, IGA_LF_2022_11, MH CZ – DRO (FNOL, 00098892), CZ.02.2.69/0.0/0.0/19_073/0016713 Disclosure of Interests None declared